Supplementary Figure 13: Novel function of DISC1 and off-target effect of Disc1-shRNA during neurodevelopment.
From: Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity
(a) A model for DISC1 functions in mature neurons. We propose that DISC1 binds ITPR1 mRNA with HZF, thereby regulating its dendritic transport for synaptic plasticity. DISC1 directly associates with a subset of mRNAs that encode synaptic proteins, including ITPR1. DISC1 forms a complex with HZF and ITPR1 mRNA, resulting in stable RNA granules. Because DISC1 can link kinesin-1 to HZF and ITPR1 mRNA, DISC1 may be involved in the conversion from static RNA granules to motile ones (namely, RNA-transporting granules). The localized mRNAs would be translated at activated spines, and then newly synthesized proteins would contribute to synaptic plasticity. (b) Phenotypic discrepancy between Disc1 knockout and knockdown. shRNA-C1 (control) or shRNA-D1 (shRNA against Disc1) knockdown vectors (provided by Dr. Song) were co-electroporated with Tα-LPL-pmKO and Tα-Cre into cerebral cortices at E15 and fixed at P1. Coronal sections were prepared and immunostained with anti-Kusabira Orange (red). Nuclei were stained with Hoechst 33342 (blue). WM, white matter. Scale bars, 50 μm.
